Synthesis of 3-aryl-4-(N-aryl)aminocoumarins via photoredox arylation and the evaluation of their biological activity.

Autor: Carneiro LSA; Departmento de Química, Pontifícia Universidade Católica do Rio de Janeiro (PUC-Rio), Rua Marquês de São Vicente 225, sala 576L, Gávea, Rio de Janeiro, RJ 20551-031, Brazil., Almeida-Souza F; Pós-graduação em Ciência Animal, Universidade Estadual do Maranhão (UEMA), Cidade Universitária Paulo VI, São Luís, MA 65055-310, Brazil; Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz (Fiocruz), Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil., Lopes YSC; Departmento de Química, Pontifícia Universidade Católica do Rio de Janeiro (PUC-Rio), Rua Marquês de São Vicente 225, sala 576L, Gávea, Rio de Janeiro, RJ 20551-031, Brazil., Novas RCV; Departmento de Química, Pontifícia Universidade Católica do Rio de Janeiro (PUC-Rio), Rua Marquês de São Vicente 225, sala 576L, Gávea, Rio de Janeiro, RJ 20551-031, Brazil., Santos KBA; Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz (Fiocruz), Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil., Ligiero CBP; Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Av. Athos da Silveira Ramos, 149, CT, Bl. A-622, Cid. Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-909, Brazil., Calabrese KDS; Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz (Fiocruz), Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil., Buarque CD; Departmento de Química, Pontifícia Universidade Católica do Rio de Janeiro (PUC-Rio), Rua Marquês de São Vicente 225, sala 576L, Gávea, Rio de Janeiro, RJ 20551-031, Brazil. Electronic address: camilla-buarque@puc-rio.br.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2021 Sep; Vol. 114, pp. 105141. Date of Electronic Publication: 2021 Jul 02.
DOI: 10.1016/j.bioorg.2021.105141
Abstrakt: A new series of 3-aryl-4-(N-aryl)aminocoumarins was synthesized in two steps starting from the natural product 4-hydroxycoumarin using the photoredox catalysis for the key step. These conditions reactions allowed to make CC bonds is up to 95% yields in mild conditions, easy operation, in an environmentally benign way, and are compatible with several patterns of substitution. The biological activity of the new compounds was tested in vitro against MCF-7, MDA-MB-231, and CCD-1072Sk cancer cell lines, as soon as to promastigotes and intracellular amastigotes of Leishmania amazonensis. Compounds 17d, 17s and 17x showed activity against promastigote forms (IC 50  = 5.96 ± 3.210, 9.05 ± 2.855 and 5.65 ± 2.078 μM respectively), and compound 17x presented the best activity against L. amazonensis amastigote intracellular form (IC 50  = 9.6 ± 1.148 μM), no BALB/c peritoneal macrophage cytotoxicity at assayed concentrations (CC 50  > 600 μM), and high selectivity to parasites over the mammalian cells (Selectivity Index > 62.2). There was no expressive activity for the cancer cell lines. Single crystal X-ray diffraction analysis was employed for structural elucidation of compounds 17a and 17s. In silico analyses of physicochemical, pharmacokinetic, and toxicological properties suggest that compound 17x is a potential candidate for anti-leishmaniasis drugs.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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